MALIGNANT METASTATIC INSULINOMA TREATED WITH STREPTOZOTOCIN

A patient with metastatic insulinoma who suffered from severe hypoglycaemic attacks was treated with 7-5 g of streptozotocin (Upjohn). Shortly after the start of treatment, the hypoglycaemic attacks ceased; fasting blood glucose levels and serum immunoreactive insulin values returned to normal upon completion of the treatment. Two years after treatment, the patient is well and active and has not had any attacks. The oral glucose tolerance test and tolbutamide stimulation test now show serum immunoreactive insulin excretion patterns similar to those seen in diabetics.     

The effect of portacaval anastomosis on oral carbohydrate tolerance and on plasma insulin levels

In patients with portal hypertension, plasma insulin levels were raised both fasting and after oral glucose or intravenous tolbutamide. This supports previous suggestions that resistance to endogenous insulin plays a major role in producing the impaired glucose tolerance found in chronic hepatic dysfunction.The operation of portacaval anastomosis was followed by impaired oral fructose tolerance, but did not significantly change oral glucose tolerance. Plasma insulin levels were unchanged by the operation, either fasting or following the stimulus of an oral glucose load or intravenous tolbutamide. The insulin response after operation was only higher after intensive pancreatic beta cell stimulation by a combination of glucose, tolbutamide, and glucagon. These results indicate that, in patients with hepatic dysfunction, little insulin is being removed by the liver from the portal blood except when the insulin secretory rate is unusually high.     

Blood glucose control and insulin secretion improved with combined therapy in type 2 diabetic patients with secondary failure to oral hypoglycaemic agents

The influence of combined therapy using insulin and oral hypoglycaemic agents on blood glucose control and on insulin secretion in Type 2 diabetic patients with secondary failure to oral hypoglycaemic agents was evaluated. Type 2 diabetic patients (n = 180) (98 normal-weight, 82 over-weight), at least 3 years from diagnosis, and having poor blood glucose control on oral hypoglycaemic agents for at least 3 months (fasting plasma glucose greater than 10.0 mmol l-1) despite intensive efforts at improvement, were included in the study. A single daily insulin injection (human ultralente), at a dose of 0.22 +/- 0.07 U kg-1 d-1 in normal-weight and 0.33 +/- 0.10 U kg-1 d-1 in over-weight patients, was added to the previous dietary and drug treatment for 6 months. A progressive and significant (2p less than 0.001) reduction of the mean daily blood glucose was observed during the first 3 months of combined therapy (from 13.2 +/- 3.2 to 8.1 +/- 2.1 mmol l-1 in normal-weight and from 13.4 +/- 3.1 to 8.8 +/- 2.3 mmol l-1 in over-weight patients), with no further significant changes thereafter. A significant increase (2p less than 0.001) in the mean daily C-peptide concentration (from 0.50 +/- 0.30 to 0.71 +/- 0.29 nmol l-1 in normal-weight and from 0.78 +/- 0.36 to 1.00 +/- 0.41 nmol l-1 in over-weight patients) took place during combined therapy. No changes of body weight (+ 1.5 +/- 1.2 kg in normal-weight and + 1.0 +/- 1.0 kg in over-weight patients) were observed.     

Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in Type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study

Secondary failure of plasma glucose control following initial successful response to diet therapy may be due to dietary indiscretion, or to progression of the intrinsic diabetic condition. We report a 10-year prospective natural history study of 432 newly diagnosed diabetic patients aged 40–69 years undertaken to assess the effect of intensive dietary management, where patients were transferred to insulin, or oral hypoglycaemic therapy (tolbutamide, metformin) by predetermined criteria of weight and plasma glucose. Secondary failure to diet therapy occurred in 41 patients in years 2–4, 67 patients in years 5–7, and 51 patients in years 8–10; 173 patients remained on diet alone until death or the end of the study. Continuation on diet alone was associated with a lower ongoing fasting plasma glucose, greater beta-cell function assessed by an oral glucose tolerance test at 6 months, and increasing age. The rate of rise of fasting plasma glucose was inversely related to the duration of successful dietary therapy, but mean weight remained constant in all groups while on diet alone. The ongoing fall in beta-cell function assessed by HOMA modelling closely mirrored the progressive rise in fasting plasma glucose: there was no change in mean insulin sensitivity in any of the groups. © 1998 John Wiley & Sons, Ltd.     

A study of carbohydrate metabolism in postnecrotic cirrhosis of liver

Intravenous glucose tolerance, insulin tolerance, tolbutamide, and glucagon tests were carried out in 21 patients with postnecrotic cirrhosis. Based arbitrarily on the bromsulphthalein retention they were divided into group A, nine patients with less impaired liver function, and group B, 12 patients with greater impairment of liver function. Intravenous glucose and insulin tolerances were reduced in both groups. The hypoglycaemic effect of tolbutamide was similar in the controls and in both groups of cirrhotic patients but this was achieved at higher plasma insulin levels in group B indicating resistance of the liver to the effect of endogenous insulin. The blood glucose response to glucagon was markedly impaired in group B patients which is consistent with this hypothesis. In contrast to the insulin response to glucose and tolbutamide, the insulin response to glucagon was reduced in the cirrhotic patients. Fasting human growth hormone and free fatty acid levels were elevated in both groups but they were not considered to be important factors in the production of insulin resistance.     

THE EFFECTS OF CYPROTERONE ACETATE AND ETHINYL OESTRADIOL ON CARBOHYDRATE METABOLISM

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti-androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.     

Glipizide versus tolbutamide,an open trial

Summary An open parallel trial with glipizide or tolbutamide was carried out in a cohort of 29 comparable maturity-onset diabetic patients. Eighteen of these individuals were studied in detail. During six months of active drug therapy the mean decrease in fasting serum glucose levels on glipizide was 25 ±2% versus 17±2% on tolbutamide (p<0.025). Decreases in post prandial glucose levels were 12.2 and 10.4%. Glucose disappearance rates (Kg) during the sixth month of treatment with both drugs increased significantly: on glipizide from 0.47±0.04%/min to 0.85±0.08%/min (p<0.005), and on tolbutamide from 0.47±0.08%/min to 0.70±0.11%/min (p<0.01). Early and late insulin release (summed increases over basal for 2–10 min and 10–60 min) during intravenous glucose tolerance testing increased during glipizide, but not during tolbutamide therapy. Post prandial insulin increments over basal during an oral glucose tolerance test also increased during glipizide, but not tolbutamide therapy. Both drugs were comparable with regard to efficacy and safety; however, only glipizide had chronic effects upon insulin secretion.     

Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice? A randomised controlled trial

We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA(1c) in newly diagnosed patients with type 2 diabetes. Secondary objectives were to compare the effects of both treatments on fasting and post-load blood glucose and insulin levels, lipids, and adverse events. Patients were randomised to receive acarbose, titrated step-wise to a maximum of 100mg three times daily (n=48) or tolbutamide, similarly titrated to a maximum of 2000 mg in three doses (n=48). The two treatments were considered equivalent if the two-sided 90% confidence interval (CI) for the difference in mean HbA(1c) levels was within the range -0.4 to 0.4%. Results were analysed on an intention-to-treat, per-protocol and on worst-case basis. Both agents reduced the HbA(1c) percentage and fasting blood glucose levels. The difference in mean decrease of HbA(1c) was 0.6% in favour of tolbutamide (90% CI 0.3, 0.9; 95% CI 0.2, 1.0). A worst-case analysis, assuming no change in HbA(1c) for dropouts, yielded a difference in mean decrease of 0.9% (90% CI 0.6, 1.2) in favour of tolbutamide. The difference in mean decrease of fasting blood glucose was 1.0 mmol/l in favour of tolbutamide (95% CI 0.3, 1.7). There were no significant differences in post-load blood glucose, fasting and post-load insulin levels, or lipids. In the acarbose group significantly more patients (15 versus 3) discontinued therapy because of adverse effects, mostly of gastrointestinal origin. We conclude that the results of this study favour tolbutamide over acarbose as first treatment for patients with newly diagnosed type 2 diabetes.     

持续气道正压通气对合并OSAHS的2型糖尿病患者动态血糖、胰岛素抵抗的影响

目的 探讨持续正压通气(CPAP)对合并OSAHS的2型糖尿病患者动态血糖、胰岛素抵抗等作用.方法 采用电脑生成随机序列方法将符合纳入排除标准的77例受试者分成两组,即实验组(常规降糖治疗+ CPAP)和对照组(常规降糖治疗),对比干预前及干预3d、1个月、3个月、6个月、12个月的空腹血糖、空腹胰岛素水平、餐后2h血糖、糖化血红蛋白、胰岛素抵抗指数、24 h内平均血糖、日平均血糖、夜间平均血糖、日间血糖波动幅度(MAGE)及夜间MAGE.结果 对照组中,干预后3d、1个月、3个月、6个月、12个月各时间段与干预前相比较,上述指标的改善差异均无统计学意义(P＞0.05).实验组中,与干预前相比较,干预后3d上述指标的改变差异无统计学意义(P＞0.05),干预1个月后空腹血糖、夜间MAGE的改善差异有统计学意义(P＜0.05),干预3个月、6个月、12个月后,动态血糖、胰岛素抵抗等改善差异均有统计学意义(P＜0.05).与干预后1个月相比较,干预3个月后夜间平均血糖、日间MAGE的改善差异有统计学意义(P＜0.05);干预6个月、12个月后胰岛素抵抗指数、24 h内平均血糖、夜间平均血糖、日间MAGE、夜间MAGE的改善差异有统计学意义(P＜0.05).结论 CPAP干预可显著改善合并2型糖尿病的OSAHS患者动态血糖、胰岛素抵抗水平,且干预时间越长,疗效越明显.     

Insulin lispro (Lys(B28), Pro(B29) in the treatment of diabetes during the fasting month of Ramadan. Ramadan Study Group.

AIMS: To compare insulin lispro with soluble human insulin in patients with Type 2 diabetes mellitus fasting during Ramadan, with respect to the rate of hypoglycaemic episodes and postprandial blood glucose values after the main meal after sunset. METHODS: The insulins were compared in an open-label, randomized, cross-over study of 70 outpatients. Hypoglycaemic episodes were recorded by the patients in a self-monitoring diary. Fasting, 1-h and 2-h postprandial blood glucose values were recorded by the patient on three consecutive days at the end of each treatment period. RESULTS: The fasting blood glucose values before sunrise (P>0.4) and after sunset (P>0.6) were similar and did not differ significantly between both treatment groups. The rise in blood glucose after the main meal after sunset was 3.0+/-0.4 mmol/l after 1 h in the insulin lispro treatment group compared to 4.3+/-0.4 mmol/l in the soluble insulin treatment group (P<0.01), and 2.6+/-0.4 mmol/l after 2h with insulin lispro compared to 4.0+/-0.5 mmol/l with soluble insulin (P<0.008). Mean hypoglycaemic episodes per patient over 14 days were 1.3+/-0.1 vs. 2.6+/-0.2, P<0.002, respectively, for insulin lispro and soluble insulin. Most hypoglycaemic episodes occurred during the time period from 6 h after the before sunrise meal until breaking the fast after sunset. CONCLUSIONS: The significantly lower rate of hypoglycaemic episodes combined with better control of postprandial blood glucose suggest insulin lispro may be more suitable prandial insulin for patients treated with Type 2 diabetes who fast during Ramadan.     

Evaluation of selected X syndrome factors during hormonal replacement therapy

Estrogen deficiency after menopause leads to characteristics changes in the hormonal profile, which may influence lipid carbohydrate and calcium-phosphate metabolism and some elements of homeostasis. AIM OF STUDY: To evaluate the influence of hormone replacement therapy with 2 mg estradiol valerate and 0,15 mg levonorgestrel on carbohydrate and lipid metabolism in women after menopause during 12 months of follow-up. We examined 101 women, mean age 52.9 +/- 4.6 years (range from 44 to 65). HRT was applied in 67 women whereas 34 women were without treatment. All of them had no carbohydrate disturbances. All women underwent clinical examination, and body mass index (BMI), fasting blood glucose, insulin, total cholesterol and triglycerides levels were obtained. At 1 and 2 hours after 75 g glucose challenge (75OGTT) glucose and insulin levels were obtained. During hormone replacement therapy all women noted release or significant decrease of climacteric symptoms. Total cholesterol level was decreased, whereas triglycerides did not change. After 12 months of treatment there was also a significant decrease of all factors relating to carbohydrate metabolism--fasting glucose and insulin, insulin/glucose ratio and area under glucose and insulin curves. In our study--after 6 months of follow-up fasting insulin level, area under glucose and insulin curves were increased whereas fasting blood glucose level remained unchanged. Among women without HRT there were no significant changes in selected lipid parameters and BMI. Triglyceride levels decreased (albeit insignificantly) but, total cholesterol levels did not change. After 12 months glucose level did not change, although other carbohydrate parameters were increased. 1) In the study group there was a statistically significant decrease in total cholesterol levels whereas triglycerides remained unchanged. 2) HRT we significantly decreased of insulin resistance and fasting blood glucose levels as compared with non-group HRT. 3) The present results indicate HRT-induced improvement of lipid and carbohydrate metabolism. 4) Long-term HRT is necessary to improve carbohydrate metabolism.     

Effects of intranasal insulin in non-obese type II diabetics

The comparative effects of intranasal and subcutaneous insulin on blood glucose and insulin levels are described in non-obese type II diabetics, in the fasting state and following a standard meal. In the fasting studies, intranasal insulin (30 units) produced a single early insulin peak. Elevated insulin levels and their hypoglycaemic effect persisted for less than 2 h whereas with subcutaneous insulin (8 units) elevated insulin levels and evidence of hypoglycaemic action were still present at 4 h. By contrast, in the meal studies both forms of insulin had similar effects on serum insulin levels and blood glucose. Moreover elevated insulin levels and evidence of reduction in post-prandial hyperglycaemia were now present at 4 h with both intranasal and subcutaneous insulin administration. Intranasal insulin in combination with a test meal now produced a biphasic insulin profile more closely resembling the normal insulin response to a meal, and reflecting the combined effects of endogenous and exogenous insulin.     

Initiation of insulin treatment after 70 years of age: patient status 2 years later.

The present study assessed 106 diabetic patients 2 years after beginning insulin treatment at or after 70 years of age. Ten patients (9%) had had the therapy discontinued after 2-4 months, 26 (25%) had died of causes unrelated to insulin therapy, 12 (11%) were lost to follow-up, and 58 (55%) were still alive and insulin treated. Fifty-one were at home and seven institutionalized for reasons unrelated to insulin therapy. Of these 58 patients, 50 were available for further study. Except for frequency of travel, which had decreased, lifestyle either improved or did not change. Patients' perceptions of the goals of treatment were more appropriate to a younger population of patients, who are less vulnerable to hypoglycaemic reactions. Mean fasting blood glucose was considered by the medical staff to be too low in 42% of cases. Adding insulin to the treatment of the elderly did not negatively affect their lifestyle, and indeed, insulin therapy appeared to create or strengthen the patients' existing social support network. Educational interventions must attempt to extend the effect of the specialized unit outside the hospital, to families, visiting nurses as well as general practitioners.     

More Uniform Diurnal Blood Glucose Control and a Reduction in Daily Insulin Dosage on Addition of Glibenclamide to Insulin in Type 1 Diabetes Mellitus: Role of Enhanced Insulin Sensitivity

Combination therapy with insulin and sulphonylurea has gained acceptance in management of subjects with Type 2 (non-insulin-dependent) diabetes mellitus. However, its role in management of Type 1 (insulin-dependent) diabetes mellitus remains controversial. In this study, the effect of combination therapy with insulin and glibenclamide on metabolic control, daily insulin dosage, and insulin sensitivity was assessed in subjects with Type 1 diabetes mellitus. Ten men with Type 1 diabetes mellitus participated in a randomized, double-blind, crossover, clinical trial with three treatment regimens, namely (1) insulin alone, (2) insulin and placebo, (3) insulin and glibenclamide, each lasting 3 months. Combination therapy induced: (1) reduction in daily insulin dosage; (2) more uniform blood glucose control as reflected by a lower average 24 h blood glucose level, a smaller difference between mean preprandial and 2 h postprandial blood glucose concentrations, decreased 24 h urine glucose excretion, and a decline in number of hypoglycaemic events; (3) improved insulin sensitivity as expressed by more rapid plasma glucose disappearance rate, without a significant alteration in fasting plasma glucagon and 1 h postprandial serum C-peptide levels; when compared with treatment with either insulin alone or with insulin and placebo. Therefore, it is apparent that the addition of glibenclamide to insulin reduces daily insulin dosage and renders a greater uniformity to diurnal blood glucose control, most probably secondary to enhancement of insulin sensitivity.     

Plasma glucagon in insulinoma

Summary Nine patients with insulinoma were studied in order to investigate glucagon levels in the fasting state and the response of plasma glucagon to tolbutamide and arginine. Fasting plasma glucagon levels were within the normal range in all patients except two cases with malignant insulinoma. Although there was no correlation between blood glucose and plasma glucagon, a significant correlation between plasma glucagon and plasma insulin was observed. No detectable changes were found in glucagon levels during tolbutamide injection. In almost all patients except one an exaggerated response of plasma glucagon was demonstrated during arginine infusion test.     

Therapy with insulin glargine (Lantus) in toddlers, children and adolescents with type 1 diabetes

OBJECTIVE: To determine the efficacy and safety of insulin glargine (IG) in children and adolescents with type 1 diabetes. In a prospective, 6-month study, 80 patients, aged 2-19 years, received IG once daily plus insulin regular or rapid analogue before meals. The data of body mass index, frequency of severe hypoglycaemia, daily mean blood glucose, fasting blood glucose, haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected. RESULTS: After 6 months, the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70% (p<0.001). Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl (p<0.05) in the total group. Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy. The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day (p<0.05). Body mass index (BMI) remained unchanged. In the 14 preschooler children, the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57% (p<0.05). CONCLUSIONS: Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes. It also improved the metabolic control in preschool-age children, without increasing the number of hypoglycaemic events.     

Comparison of tolbutamide and metformin in elderly diabetic patients

In a randomized double-blind cross-over study the efficacy, metabolic effects, and acceptability of metformin were compared with tolbutamide in 20 diabetic patients aged between 65 and 95 years. No significant differences were noted after treatment in blood glucose control (fasting plasma glucose, metformin 9.1 +/- 2.8 mmol l-1, tolbutamide 8.3 +/- 2.8 mmol l-1; mean change, metformin +1.1 mmol l-1, tolbutamide +0.02 mmol l-1, p = 0.215), domiciliary blood glucose control, fasting insulin, lactate, cholesterol or triglyceride levels. There was a significant difference in weight change between the two treatments (on metformin -2.0 kg, from 63.2 +/- 11.8 to 61.2 +/- 12.3; on tolbutamide, +1.6 kg, from 61.4 +/- 11.1 to 63.0 +/- 12.3; p = 0.001). Initial gastro-intestinal side-effects occurred in 30% of patients with metformin. These were transient and responded to temporary reduction in treatment dosage. Metformin could not be distinguished from tolbutamide in elderly diabetic patients, except in that it was associated with weight loss.     

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.     

The behaviour of insulinaemia in patients with liver cirrhosis after intravenous administration of glucose,tolbutamide and glucagon

Summary The response of both blood glucose and serum immunoreactive insulin to glucagon, glucose and tolbutamide was studied in ten patients with welldocumented, advanced liver cirrhosis and in ten healthy subjects without history indicative of liver impairment or diabetes. Glucose was administered as a rapid intravenous injection in a dose of 0.33 g/kg of body weight, tolbutamide in a dose of 1.0 g and glucagon in a dose of 1.0 mg. The mean fasting serum insulin levels of cirrhotic patients did not differ significantly from the values obtained in healthy subjects. However, after administration of glucose or tolbutamide the rise of insulinaemia was significantly higher in cases of liver cirrhosis than in normal subjects. The increase of serum insulin values after intravenous administration of glucagon was similar in both groups; thus glucagon failed to induce hyperinsulinaemia as observed after glucose or tolbutamide. The possible causes of this phenomenon have been discused.Report presented at the 6th Meeting of the European Association for Study of Diabetes, Warsaw, 23rd to 25th September 1970.     

Effects of propranolol on blood sugar,insulin and free fatty acids

Summary Three types of experiment were carried out in normal subjects to determine the effect of therapeutic doses of oral Propranolol on 1. the blood sugar, plasma insulin and free fatty acids (FFA) during prolonged fasting and exercise, 2. intravenous glucose tolerance and the rise in insulin level after intravenous glucose, and 3. the intravenous glucose tolerance on exercise. Propranolol caused only slight lowering of the blood sugar in normals, even after 24 h fasting. This was most noticeable during exercise. There was no significant effect of Propranolol on fasting insulin levels, on glucose tolerance at rest or exercise, or on the response of plasma insulin levels to intravenous glucose. Lowering of plasma FFA levels was found in all subjects when taking Propranolol particularly during and after exercise. Possible mechanisms of hypoglycaemia in those cases reported in the literature are discussed. It is concluded that hypoglycaemia is not a major problem in Propranolol therapy.These studies were carried out as part of an elective period in the Departments of Medicine and Experimental Pathology in the University of Birmingham.